1. Field of the Invention
The present invention relates generally to liquid chalcogenide compositions, more particularly to stable liquid pharmaceutical compositions comprising chalcogenides. The invention further relates to the use of such compositions to protect cells and animals from injury, disease, and premature death.
2. Description of the Related Art
Compounds containing a chalcogen element, i.e., those in Group 6 of the periodic table, but excluding oxides, are commonly termed “chalcogenides” or “chalcogenide compounds.” These elements are sulfur (S), selenium (Se), tellurium (Te) and polonium (Po). Common chalcogenides contain one or more of S, Se, and Te, in addition to other elements.
It has been recently shown that treatment with chalcogenides induces stasis of biological matter and protects biological matter from hypoxic and ischemic injury. In these studies, it was demonstrated that hydrogen sulfide (H2S) gas, a potent inhibitor of oxygen consumption, can reduce metabolism and protect mice and rats from hypoxic injuries (PCT Publication No. WO2005/041655). Although hydrogen sulfide gas has not been typically considered a medical gas, this unexpected result presents exciting possibilities for the treatment or prevention of a number of animal and human diseases, particularly hypoxia and ischemia-related diseases and injuries.
Certain chalcogenide compounds (e.g., hydrogen sulfide and hydrogen selenide), are not stable in the presence of oxygen due to their ability to react chemically with oxygen, leading to their oxidation and chemical transformation. For example, the chemical transformation of sulfide limits its use as a pharmaceutical due to limited stability, limited shelf-life, and the potential for the introduction of oxidation products during manufacture, storage, or use. Potential oxidizing agents of sulfide include oxygen, carbon dioxide, and inherent metal impurities that can produce a mixture of oxidation products (e.g., sulfite, sulfate, thiosulfate, polysulfides, dithionate, polythionate, and elemental sulfur). Thus, the rapid oxidation of sulfide during storage limits its use as a pharmaceutical agent.
To provide a pharmaceutical benefit to a cell or patient in need of treatment with a chalcogenide, finished dosage forms that are stable, easily and reproducibly manufactured, and designed for standard routes of administration are needed. Clearly, there is a need in the art for stable, liquid pharmaceutical compositions of chalcogenides, including those containing sulfide. Sulfide is defined as sulfur in its −2 valence state, either as H2S or as a salt thereof (e.g., NaHS, Na2S, etc.) that may be conveniently administered to patients, both in a controlled medical environment e.g., for treatment of disease, as a treatment in the field during an emergency, or in critical care in response to a catastrophic injury or life-threatening medical event. The present invention meets this need by providing novel, stable, liquid pharmaceutical compositions of chalcogenides, which are demonstrated herein to protect animals from injury and death resulting from hypoxic and/or ischemic conditions, as well as other injuries and disease conditions.